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07Undated
History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does. The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome. And human history has, in turn, selected genomes that carry these impulses, ambitions, fantasies, and desires. This self-fulfilling circle of logic is responsible for some of the most magnificent and evocative qualities in our species, but also some of the most reprehensible. It is far too much to ask ourselves to escape the orbit of this logic, but recognizing its inherent circularity, and being skeptical of its overreach, might protect the week from the will of the strong, and the 'mutant' from being annihilated by the 'normal'.
Siddhartha Mukherjee / quote
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08Undated
If the history of the last century taught us the dangers of empowering governments to determine genetic “fitness” (i.e., which person fits within the triangle, and who lives outside it), then the question that confronts our current era is what happens when this power devolves to the individual. It is a question that requires us to balance the desires of the individual— to carve out a life of happiness and achievement, without undue suffering— with the desires of a society that, in the short term, may be interested only in driving down the burden of disease and the expense of disability. And operating silently in the background is a third set of actors: our genes themselves, which reproduce and create new variants oblivious of our desires and compulsions— but, either directly or indirectly, acutely or obliquely, influence our desires and compulsions. Speaking at the Sorbonne in 1975, the cultural historian Michel Foucault once proposed that “a technology of abnormal individuals appears precisely when a regular network of knowledge and power has been established.” Foucault was thinking about a “regular network” of humans. But it could just as easily be a network of genes.
Siddhartha Mukherjee / quote
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15Undated
McKusick's belief in this paradigm-the focus on disability rather than abnormalcy-was actualized in the treatment of patients in his clinic. Patients with dwarfism, for instance, were treated by an interdisciplinary team of genetic counselors, neurologists, orthopedic surgeons, nurses, and psychiatrists trained to focus on specific disabilities of persons with short stature. Surgical interventions were reserved to correct specific deformities as they arose. The goal was not to restore "normalcy"-but vitality, joy, and function. McKusic had rediscovered the founding principles of modern genetics in the realm of human pathology. In humans as in wild flies, genetic variations abounded. Here too genetic variants, environments, and gene-environment interactions ultimately collaborated to cause phenotypes-except in this case, the "phenotype" in question was disease. Here too some genes had partial penetrance and widely variable expressivity. One gene could cause many diseases, and one disease could be caused by many genes. And here too "fitness" could not be judged in absolutes. Rather the lack of fitness-illness [italicized, sic] in colloquial terms- was defined by the relative mismatch between an organism and environment.
Siddhartha Mukherjee / quote
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16Undated
When scientists underestimate complexity, they fall prey to the perils of unintended consequences. The parables of such scientific overreach are well-known: foreign animals, introduced to control pests, become pests in their own right; the raising of smokestacks, meant to alleviate urban pollution, releases particulate effluents higher in the air and exacerbates pollution; stimulating blood formation, meant to prevent heart attacks, thickens the blood and results in an increased risk of blood clots in the heart. But when nonscientists overestimate [italicized, sic] complexity- 'No one can possibly crack this [italicized, sic] code" - they fall into the trap of unanticipated consequences. In the early 1950s , a common trope among some biologists was that the genetic code would be so context dependent- so utterly determined by a particular cell in a particular organism and so horribly convoluted- that deciphering it would be impossible. The truth turned out to be quite the opposite: just one molecule carries the code, and just one code pervades the biological world. If we know the code, we can intentionally alter it in organisms, and ultimately in humans. Similarly, in the 1960s, many doubted that gene-cloning technologies could so easily shuttle genes between species. by 1980, making a mammalian protein in a bacterial cell, or a bacterial protein in a mammalian cell, was not just feasible, it was in Berg's words, rather "ridiculously simple." Species were specious. "Being natural" was often "just a pose.
Siddhartha Mukherjee / quote
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20Undated
When a disease insinuates itself so potently into the imagination of an era, it is often because it impinges on an anxiety latent within that imagination. AIDS loomed so large on the 1980s in part because this was a generation inherently haunted by its sexuality and freedom; SARS set off a panic about global spread and contagion at a time when globalism and social contagion were issues simmering nervously in the West. Every era casts illness in its own image. Society, like the ultimate psychosomatic patient, matches its medical afflictions to its psychological crises; when a disease touches such a visceral chord, it is often because that chord is already resonating.
Siddhartha Mukherjee / quote
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23Undated
In an essay titled A View From the Front Line, Jencks described her experience with cancer as like being woken up midflight on a jumbo jet and then thrown out with a parachute into a foreign landscape without a map:"There you are, the future patient, quietly progressing with other passengers toward a distant destination when, astonishingly (Why me?) a large hole opens in the floor next to you. People in white coats appear, help you into a parachute and — no time to think — out you go."You descend. You hit the ground....But where is the enemy? What is the enemy? What is it up to?...No road. No compass. No map. No training. Is there something you should know and don't?"The white coats are far, far away, strapping others into their parachutes. Occasionally they wave but, even if you ask them, they don't know the answers. They are up there in the Jumbo, involved with parachutes, not map-making.
Siddhartha Mukherjee / quote
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